Bone and cartilage are sensitive to alterations that result in age-associated diseases such as osteoporosis and osteoarthritis. We are studying the regulation of matrix genes expressed by chondrocytes and related cells. Type II collagen is important for cartilage function and we have identified DNA sequences that are responsible for the chondrocyte-specific expression of this gene. Initial studies indicate that chondrocytes contain unique patterns of DNA binding proteins that are different from those obtained from prechondrogenic mesenchyme cells. Next, we will identify the target DNA sequence for these chondrocyte-specific proteins as the first step in the isolation, characterization, and cloning of these proteins. In addition, we are studying the regulation of the cartilage proteoglycan gene by vitamin D. This may serve as model system for analyzing the molecular action of this important hormone involved in bone formation. A third project involves the regulation of collagen and collagenase gene expression in synovial cells isolated from osteoarthritis (OA) or rheumatoid arthritis (RA) patients and the response of these cells to cytokines. Interleukin-1 induces collagenase mRNA in both cell types with the induction occurring to a greater extent in RA versus OA synovial fibroblasts. other projects are ongoing assessing the histopathology of articular cartilage in aging Wistar rats and examining the induction of stem cell proliferation and differentiation in bone.